Through the NIH Shared Instrument Grant program funds are requested for a replacement of a 25-year old Bruker 500 MHz magnet and console with a new Agilent 500 MHz magnet and console. The current high- resolution, liquid-state NMR system is located in the basement of the Yale Magnetic Resonance Research Center, which is part of the premiere research building, The Anlyan Center, of the Yale School of Medicine. Frequent and repeated hardware failings, as well as stability and homogeneity issues of the old hardware makes a near future replacement mandatory in order to guarantee continued productivity on a large number of NIH-funded grants. The current 500 MHz system is the workhorse for a wide range of biochemical studies closely related to in vivo MR projects. These include, but are not limited to, the measurement of blood substrate levels and 13C fractional enrichments, the development of novel isotopically-labeled substrates and the detection of metabolite turnover in rodent brain extract samples. While many of the high-resolution applications can be labeled as routine, they are of critical importance in providing supporting information for many state-of-the-art in vivo metabolic studies, both in humans and rodents. Besides a new 500 MHz magnet and console, additional funds are requested for an auto-tunable RF probe with XYZ gradients and an automated sample changer. This combination is essential to achieve the highest productivity and system utilization by allowing hundreds of similar samples to be loaded, tuned, shimmed and measured automatically, during both night and weekend time slots. The current 500 MHz NMR system supports twelve active NIH grants, with three pending grants potentially using the system in the near future. A successful replacement of the current 500 MHz high-resolution NMR system with a new 500 MHz system will provide essential support to these NIH grants and will thereby guarantee continued productivity and innovation.